Microbiota & Arthritis Development

A recent review performed at the centre for Immunobiology at the University of Glasgow has been looking at whether disruptions to the microbiome could be a causative factor in the development of rheumatoid arthritis (RA), an auto-immune condition which causes pain and swelling in the joints. The researchers reviewed a number of clinical studies, looking firstly at whether RA sufferers display an imbalance in gut flora or not. They then secondly, reviewed clinical trials that have attempted to manipulate the microbiome through the use of probiotics, to assess whether or not probiotics could be a useful supplement option for the condition.

Within this article:

• A closer look at the microbiome:
• Manipulating the microbiome:

A closer look at the microbiome:

The researchers reviewed numerous studies and found that alterations in the intestinal microbiota are generally associated with arthritis, however different studies implicate different species of bacteria in the disease process. Some suggest that high levels of Prevotella could be indicative of RA for example (visit the Glossary for more information on Prevotella), whereas others found low levels of Bacteroides or Akkermansia to be prevalent in people with the condition.

One study by Shar et al¹ detected increases in Prevotella and Leptotrichia species, with a reduction in Bacteroides species, in the stool samples from patients with recent onset of RA. However these findings are in direct conflict with findings from two independent studies, by Vaahtovuo et al² and Liu et al³ which reported an increase in Lactobacillus salivarius and L. ruminis, with a decrease in Prevotella species.

All the studies reviewed did show changes to RA sufferers microbial communities, however a pattern is yet to be found as to which species could be having a causative effect on disease onset and progression.

Other research discovered that Prevotella copri was found in higher numbers in 75% of patients recently diagnosed compared to 21.4% of healthy individuals, 11.5% in those with more long-term rheumatoid conditions and 37.5% of those with an alternative form of arthritis⁵.

Manipulating the microbiome:

Given that alterations to the intestinal microbiota have been found in patients with RA, it has been suggested that modifying the flora  with probiotics might be a valuable therapeutic strategy. Early trials using animal models showed some encouraging results, however these are yet to be replicated in human models.

Interestingly, some trials have shown improvements in pathology markers, such as markers of inflammation, however those improved plasma markers have not translated in to clinical, or symptomatic improvements. A study by Malin et al⁴ showed that juvenile patients treated with L. rhamnosus GG ((LGG^®) showed an increase in Immunoglobulin A (a marker of immunity), and a decrease in TNF (tumour necrosis factor), a marker of inflammation. Even despite these clinical improvements however, the patients being treated had no real improvement in their symptoms or pain levels, thus the probiotic intervention was deemed not to be of clinical benefit. Health professionals can visit this strain's entry in the Probiotics Database to read more about the research using L. rhamnosus GG ((LGG^®).

Trials of probiotics in arthritis have therefore yielded fairly disappointing results, and more in-depth research is certainly still needed. In particular it is felt that study participant ages should be taken in to account when the studies are designed, as our microbial populations change as we age which adds another degree of complexity to the trial results.

Having said that, we think it's fascinating to see the increasing plethora of seemingly unrelated health conditions being linked to gut bacteria, so will continue to watch this space with anticipation. We do know that auto-immune conditions are increasingly being linked to gut permeability or 'leaky gut'; scientists believe that the weakening of the mucosal barrier (which probiotics are thought to play a significant part in maintaining) is a pivotal factor in the development of auto-immune diseases. It may therefore make sense to support your gut health or those with auto-immune diseases. Health professionals can visit our Professionals site to find out more about leaky gut, how gut bacteria may affect auto-immunity, or probiotics and the immune system.

References

1. Scher JU, Ubeda C, Equinda M, et al. Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum 2012; 64:3083–3094.
2. Vaahtovuo J, Munukka E, Korkeamäki M, et al. Fecal microbiota in early rheumatoid arthritis. J Rheumatol 2008; 35:1500–1505.
3. Liu X, Zou Q, Zeng B, et al. Analysis of fecal Lactobacillus community structure in patients with early rheumatoid arthritis. Curr Microbiol 2013; 67:170–176.
4. Malin M, Verronen P, Korhonen H, et al. Dietary therapy with Lactobacillus GG, bovine colostrum or bovine immune colostrum in patients with juvenile chronic arthritis: evaluation of effect on gut defence mechanisms. Inflammopharmacology 1997; 5:219–236.
5. Scher J U, Sczesnak A, Longman R S et al. “Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis”. Published online, open access eLife Nov 2013.
6. Yinxi He & Yanxia Chen (2022) The potential mechanism of the microbiota-gut-bone axis in osteoporosis: a review. Osteoporosis International, 33: 495–2506.
7. Pereira L & Monterio R (2022) Tailoring gut microbiota with a combination of Vitamin K and probiotics as a possible adjuvant in the treatment of rheumatic arthritis: a systematic review. Clinical Nutrition, Vol 51: 37-49.